Biology subjects

Nielsen, J. R.

Publications and source records attributed to Nielsen, J. R..

3 recordsLinked to original sources

bioRxiv2026

No-known-vector flaviviruses exhibit diverse replication and virulence phenotypes in mice

The Orthoflavivirus genus (flaviviruses) includes globally significant arboviruses, which cycle between arthropod vectors (mosquitoes and ticks) and vertebrate hosts. In contrast, no-known-vector flaviviruses (NKVFVs) have been isolated from rodents and bats, but not arthropods, so are thought to spread by vector-independent routes. However, little is known about the host range and pathogenic mechanisms of these viruses. To evaluate NKVFV pathogenesis, we infected wild-type, Ifnar1-/-, and Ifnar1-/- Ifngr1-/- mice by footpad inoculation with 12 NKVFVs: Entebbe bat virus (ENTV), Sokuluk virus (SOKV), Yokose virus (YOKV), Modoc virus (MODV), Apoi virus (APOIV), Jutiapa virus (JUTV), Sal Vieja virus (SVV), Dakar bat virus (DBV), Rio Bravo virus (RBV), Montana myotis leukoencephalitis virus (MMLV), Phnom Penh bat virus (PPBV), and Tamana bat virus (TABV). We compared these NKVFVs to the mosquito-borne Zika virus and Kedougou virus and to the tick-borne Langat virus and Kadam virus. We monitored disease signs and measured viremia. 7 NKVFVs (ENTV, SOKV, YOKV, MODV, APOIV, DBV, RBV) were virulent in Ifnar1-/- mice, causing 100% lethality within 9 dpi, accompanied by viremia. All viruses tested were virulent in Ifnar1-/- Ifngr1-/- mice and produced greater viremia compared to Ifnar1-/- mice. No viremia or disease signs were detected in wild-type mice. We further evaluated RBV, MMLV, and PPBV replication in mouse primary fibroblasts and bone marrow-derived macrophages, as well as in cell lines from three bat species. Altogether, our results provide new information about the virulence and replication phenotypes of NKVFVs, supporting future studies investigating NKVFV-specific and pan-flavivirus pathogenic mechanisms. IMPORTANCEFlaviviruses that cause human disease are transmitted by mosquitoes and ticks (e.g. West Nile virus, yellow fever virus, tick-borne encephalitis virus). But there are related flaviviruses that are not known to infect arthropods, so are thought to spread by vector-independent routes (no-known-vector flaviviruses, NKVFVs). Not much is known about NKVFVs, but they provide an opportunity to understand flavivirus replication, tropism, and pathogenesis more broadly. We evaluated a panel of 12 NKVFVs for their ability to cause disease in mice with and without antiviral interferon responses as well as their replication in mouse cells. Our findings provide new information about these under-studied viruses and demonstrate which mouse models may be appropriate to use for further studies with NKVFVs.

microbiology↗

bioRxiv2020

Implementing the precautionary approach into fisheries management: Making the case for probability-based harvest control rules

The precautionary approach to fisheries management advocates for risk-averse management strategies that include biological reference points as well as decision rules and account for scientific uncertainty. In this regard, two approaches have been recommended: (i) harvest control rules (HCRs) with threshold reference points to safeguard against low stock biomass, and (ii) the P* method, a probability-based HCR that reduces the catch limit as a function of scientific uncertainty (i.e. process, model, and observation uncertainty). This study compares the effectiveness of these precautionary approaches in recovering over-exploited fish stocks with various life-history traits and under a wide range of levels of scientific uncertainty. We use management strategy evaluation based on a stochastic, age-based operating model with quarterly time steps and a stochastic surplus production model. The results show that the most effective HCR includes both a biomass threshold as well as the P* method, and leads to high and stable long-term yield with a decreased risk of low stock biomass. For highly dynamics stocks, management strategies that aim for higher biomass targets than the traditionally used BMSY result in higher long-term yield. This study makes the case for probability-based HCRs by demonstrating their benefit over deterministic HCRs and provides a list of recommendations regarding their definition and implementation.

ecology↗

bioRxiv2020

RuBisCO adaptation is more limited by phylogenetic constraint than by catalytic trade-off

Rubisco assimilates CO2 to form the sugars that fuel life on earth. Correlations between rubisco kinetic traits across species have led to the proposition that rubisco adaptation is highly constrained by catalytic trade-offs. However, these analyses did not consider the phylogenetic context of the enzymes that were analysed. Thus, it is possible that the correlations observed were an artefact of the presence of phylogenetic signal in rubisco kinetics and the phylogenetic relationship between the species that were sampled. Here, we conducted a phylogenetically-resolved analysis of rubisco kinetics and show that there is a significant phylogenetic signal in rubisco kinetic traits. We re-evaluated the extent of catalytic trade-offs accounting for this phylogenetic signal and found that all were attenuated. Following phylogenetic correction, the largest catalytic trade-offs were observed between the Michaelis constant for CO2 and carboxylase turnover ([~]21-37 %), and between the Michaelis constants for CO2 and O2 ([~]9-19 %), respectively. All other catalytic trade-offs were substantially attenuated such that they were marginal (<9 %) or non-significant. This phylogenetically resolved analysis of rubisco kinetic evolution also identified kinetic changes that occur concomitant with the evolution of C4 photosynthesis. Finally, we show that phylogenetic constraints (most likely caused by a slow rate of molecular evolution) have played a larger role than catalytic trade-offs in limiting the evolution of rubisco kinetics. Thus, although there is strong evidence for some catalytic trade-offs, rubisco adaptation has been more limited by phylogenetic constraint than by the combined action of all such trade-offs.

plant biology↗